Alcoholism is a multi-faced disease with many different etiologies. No single approach to treatment has been universally successful. The Charleston Alcohol Research Center at the Medical University of South Carolina has the research goal of improving treatment for people suffering from alcohol abuse and behavioral neuroscience and pharmacotherapy were assembled to a research team poised to take on the challenge of working together to identify promising new pharmacological treatments for alcoholism and its comorbid disorders. The Center funding mechanism afforded the opportunity for collaborative, and more importantly, provided the researchers both Core support and organizational infrastructure to facilitate their productivity. It also provided a source of funding for pilot projects to bring new investigators as well as new technology to the Center. The improved communication and interaction between Center investigators accomplished the expected result of attracting new investigators into the alcohol research areas as well as stimulating the acquisition of extramural funding for new and collaborative research projects. The original administrative/scientific leaders continue to occupy leadership positions, and the original five senior level researchers are involved in the renewal. These investigators are joined in their renewal projects by junior faculty or faculty new to alcohol research in a "team" approach. The threat that ties all the research components together in the Center is pharmacotherapy. The projects are interdigitated as closely as possible between a human and a animal counterpart. Research Components 1 and 2 involve evaluation of medications and combinations of medications on alcohol ingestion and reward in humans and animals, respectively. Finally, Research Component 5 examines the role of stress and a medication that may act by modifying the stress response on alcohol craving in humans with comorbid alcoholism and Post Traumatic Stress Disorder. The Lopez Pilot Project is the animal counterpart to this study. In this renewal application, neuroimaging technology has been introduced to the Center, as has the acoustic startle response, electrophysiology, and molecular biology. The Charleston Alcohol Research Center is well positioned to evaluate promising compounds in animal models, in a human laboratory setting, and in clinical trials.